It is well known that females at the time of menopause suffer a marked loss of bone mass giving rise ultimately to osteopenia, which in turn gives rise to spontaneous crush fractures of the vertebrae and fractures of the long bones. This disease is generally known as postmenopausal osteoporosis and presents a major medical problem, both in the United States and most other countries where the life-span of females reaches ages of at least 60 and 70 years. Generally the disease, which is often accompanied by bone pain and decreased physical activity, is diagnosed by one or two vertebral crush fractures with X-ray evidence of diminished bone mass. It is known that this disease is accompanied by diminished ability to absorb calcium, decreased levels of sex hormones, especially estrogen and androgens, and a negative calcium balance.
Methods for treating the disease have varied considerably but to date no really satisfactory treatment is yet known. For example, calcium supplementation by itself has not been successful in preventing or curing the disease and the use of sex hormones, especially estrogen, which has been reported to be effective in preventing the rapid loss of bone mass experienced in postmenopausal women, has been complicated by the tear of its possible carcinogenicity. Other treatments, for which variable results have again been reported, have included a combination of vitamin D in large doses, calcium and fluoride. The primary problem with this approach is that fluoride induces structurally unsound bone, called woven bone, and in addition, produces a number of side effects such as increased incidence of fractures and gastrointestinal reaction to the large amounts of fluoride administered.
U.S. Pat. No. 4,725,596 discloses methods for treating or preventing metabolic bone disease characterized by the loss of bone mass by administering at least one compound having the formulae (I) and (II): ##STR1## where R.sub.1, R.sub.2 and R.sub.3 are each selected from the group consisting of hydrogen, hydroxyl, lower alkyl, acyl and O-alkyl and R.sub.3 is selected from the group consisting of hydrogen, hydroxyl, keto, lower alkyl, acyl and O-alkyl.
See also, Tilyard, M. W. et al., N. Eng. J. Med. 326:357-362 (1992) and Caniggia. A., et al., Metabolism 39:43-49 (1990), who disclose the treatment of osteoporosis with calcitriol (1.alpha.,25-dihydroxyvitamin D.sub.3). However, this method has the significant disadvantage that high levels of these compounds, e.g., 1.alpha.,25-dihydroxyvitamin D.sub.3, causes an increase of the blood calcium level above the normal range and concomitant toxicity.
U.S. Pat. No. 4,410,515 discloses the following compounds having Formula (Ill) which are active in maintaining calcium and phosphorus metabolism and are useful for treating hypocalcemia in animals: ##STR2## wherein the double bond between positions C-22 and C-23 is single or double; R.sup.2 is hydrogen, CH.sub.3 or CH.sub.2 CH.sub.3 ; X is selected from the group consisting of hydrogen and --OR.sup.1, where R.sup.1 is hydrogen or a straight or branched chain glycosidic residue containing 1-20 glycosidic units per residue; with the proviso that at least one of the R.sup.1 is glycosidic residue.